tbuckley/cabot-search huggingface dataset:
Converting adults with sickle cell disease from full agonist opioids to buprenorphine: A reliable method with safety and early evidence of reduced acute care utilization
Authors: Mandy S. David, Jennifer Jones, Ashley Lauriello, Ijeoma Nnake, Manuela Plazas Montana, Kyra Lasko, Carlos Buri‐Nagua, Yetunde Olagbaju, Elizabeth Williams, Matthew Sears, Benjamin Salzberg, Sophie M. Lanzkron, C. Patrick Carroll
Journal: American Journal of Hematology (2022)

Abstract Buprenorphine, a novel opioid with complex pharmacology, is effective for treating pain and is qualitatively safer than high‐dose full agonist opioid therapy; but transitioning to buprenorphine can be technically complex and carries some risk of precipitated withdrawal. We report our clinic's experience converting 36 patients with sickle cell disease (SCD) from full agonist opioids to buprenorphine using a method developed in the past 10 years. Thirty of these patients were induced using a standard outpatient protocol and six were induced during medical admissions. Typically, patients were on high‐dose chronic opioid therapy (COT) with inadequate response, and often with very high acute care utilization. Unlike prior case series, the method of induction, dosing, and management of withdrawal are detailed, as are post‐induction adverse events. There were seven adverse events in the first 3 days following standard induction, and two of which were judged to be definitely related to the induction but none with any lasting sequelae. At 6 months follow‐up, five participants had discontinued buprenorphine (16.67%), and overall acute care visits dropped from a mean of 10.50 (SD 11.35) in the 6 months pre‐induction to 2.89 (SD 3.40) in the 6 months post‐induction. In an appropriately interdisciplinary care setting, buprenorphine shows promise as a safe alternative to COT with early evidence of benefit for high‐utilizing patients with SCD.
Comparative Risk of Serious Infections With Biologic Agents and Oral Small Molecules in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis
Authors: Virginia Solitano, Antonio Facciorusso, Tine Jess, Christopher Ma, Cesare Hassan, Alessandro Repici, Vipul Jairath, Alessandro Armuzzi, Siddharth Singh
Journal: Clinical Gastroenterology and Hepatology (2022)
PHOX2B is a Sensitive and Specific Marker for the Histopathological Diagnosis of Pheochromocytoma and Paraganglioma
Authors: Minami Miyauchi, Takumi Akashi, Asuka Furukawa, Keisuke Uchida, Tomoki Tamura, Noboru Ando, Susumu Kirimura, Hiroshi Shintaku, Kurara Yamamoto, Takashi Ito, Keiko Miura, Kou Kayamori, Yosuke Ariizumi, Takahiro Asakage, Atsushi Kudo, Minoru Tanabe, Yasuhisa Fujii, Hironori Ishibashi, Kenichi Okubo, Masanori Murakami, Tetsuya Yamada, Akira Takemoto, Yuan Bae, Yoshinobu Eishi, Kenichi Ohashi
Journal: Endocrine Pathology (2022)
Blood-Pressure Targets in Comatose Survivors of Cardiac Arrest
Authors: Jesper Kjaergaard, Jacob E. Møller, Henrik Schmidt, Johannes Grand, Simon Mølstrøm, Britt Borregaard, Søren Venø, Laura Sarkisian, Dmitry Mamaev, Lisette O. Jensen, Benjamin Nyholm, Dan E. Høfsten, Jakob Josiassen, Jakob H. Thomsen, Jens J. Thune, Laust E.R. Obling, Matias G. Lindholm, Martin Frydland, Martin A.S. Meyer, Matilde Winther-Jensen, Rasmus P. Beske, Ruth Frikke-Schmidt, Sebastian Wiberg, Søren Boesgaard, Søren A. Madsen, Vibeke L. Jørgensen, Christian Hassager
Journal: New England Journal of Medicine (2022)

Evidence to support the choice of blood-pressure targets for the treatment of comatose survivors of out-of-hospital cardiac arrest who are receiving intensive care is limited.
Oxygen Targets in Comatose Survivors of Cardiac Arrest
Authors: Henrik Schmidt, Jesper Kjaergaard, Christian Hassager, Simon Mølstrøm, Johannes Grand, Britt Borregaard, Laust E. Roelsgaard Obling, Søren Venø, Laura Sarkisian, Dmitry Mamaev, Lisette O. Jensen, Benjamin Nyholm, Dan E. Høfsten, Jakob Josiassen, Jakob H. Thomsen, Jens J. Thune, Matias G. Lindholm, Martin A. Stengaard Meyer, Matilde Winther-Jensen, Marc Sørensen, Martin Frydland, Rasmus P. Beske, Ruth Frikke-Schmidt, Sebastian Wiberg, Søren Boesgaard, Vibeke Lind Jørgensen, Jacob E. Møller
Journal: New England Journal of Medicine (2022)

The appropriate oxygenation target for mechanical ventilation in comatose survivors of out-of-hospital cardiac arrest is unknown.In this randomized trial with a 2-by-2 factorial design, we randomly assigned comatose adults with out-of-hospital cardiac arrest in a 1:1 ratio to either a restrictive oxygen target of a partial pressure of arterial oxygen (Pao2) of 9 to 10 kPa (68 to 75 mm Hg) or a liberal oxygen target of a Pao2 of 13 to 14 kPa (98 to 105 mm Hg); patients were also assigned to one of two blood-pressure targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with severe disability or coma (Cerebral Performance Category [CPC] of 3 or 4; categories range from 1 to 5, with higher values indicating more severe disability), whichever occurred first within 90 days after randomization. Secondary outcomes were neuron-specific enolase levels at 48 hours, death from any cause, the score on the Montreal Cognitive Assessment (ranging from 0 to 30, with higher scores indicating better cognitive ability), the score on the modified Rankin scale (ranging from 0 to 6, with higher scores indicating greater disability), and the CPC at 90 days.A total of 789 patients underwent randomization. A primary-outcome event occurred in 126 of 394 patients (32.0%) in the restrictive-target group and in 134 of 395 patients (33.9%) in the liberal-target group (hazard ratio, 0.95; 95% confidence interval, 0.75 to 1.21; P = 0.69). At 90 days, death had occurred in 113 patients (28.7%) in the restrictive-target group and in 123 (31.1%) in the liberal-target group. On the CPC, the median category was 1 in the two groups; on the modified Rankin scale, the median score was 2 in the restrictive-target group and 1 in the liberal-target group; and on the Montreal Cognitive Assessment, the median score was 27 in the two groups. At 48 hours, the median neuron-specific enolase level was 17 μg per liter in the restrictive-target group and 18 μg per liter in the liberal-target group. The incidence of adverse events was similar in the two groups.Targeting of a restrictive or liberal oxygenation strategy in comatose patients after resuscitation for cardiac arrest resulted in a similar incidence of death or severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).
Poster Session Group III – Green TPS 39
Authors: Sébastien Lefèvre, Sandrine Jacquenet, C. Richard, K. Astafieff, L. Peru, Yann Froelicher, Gisèle Kanny
Journal: Allergy (2015)

their TSS score was 6.4 AE 3.3 in 15 and 25.9% of them had a value > 8 corresponding to a major symptomatology.Cluster analysis identified among all patients the existence of a homogeneous group of patients characterized by a more significant ocular involvement (TSSS: 8,5 AE vs 4,6 AE 2,7 P < 0.0001;TOSS: 60,3 AE 16.0 vs 25,8 AE 14.1 P < 0.0001) whose rhinitis was more frequently persistent with a moderate to severe intensity (61.4% vs 39.0% P < 0.0001), and with a greater impairment of the quality of life (3.5 AE 1.0 vs 2.5 AE 1.0 P < 0.0001).The logistic regression analysis confirmed these data showing also that pollen but also fungal spore allergens are more frequently identified.In these patients the practitioners more frequently associated intranasal corticosteroids (73.9% vs 67.6% P < 0.001) and cromones (76.0%vs 52.6% P < 0.0001) with oral H1 antihistamines, Conclusion: The association of rhinitis and ocular symptoms could be a frequent and specific entity requiring a specific treatment combining oral H1 antihistamines and cromones.
Mitochondrial DNA is a major source of driver mutations in cancer
Authors: Minsoo Kim, Mahnoor Mahmood, Ed Reznik, Payam A. Gammage
Journal: Trends in cancer (2022)

Somatic mutations to mitochondrial DNA (mtDNA) in cancers are abundant, but their selection is highly gene and context dependent.Truncating and tRNA mutations to mtDNA are drivers in certain diseases, but the function of the vast majority of somatic mtDNA variants is uncharacterized.Heteroplasmic dosage is likely a critical determinant of the phenotype produced by somatic mtDNA mutations.New techniques for single-cell profiling technologies and mitochondrial genome editing overcome the key obstacles to delineating the function of mtDNA mutations in cancer. Mitochondrial DNA (mtDNA) mutations are among the most common genetic events in all tumors and directly impact metabolic homeostasis. Despite the central role mitochondria play in energy metabolism and cellular physiology, the role of mutations in the mitochondrial genomes of tumors has been contentious. Until recently, genomic and functional studies of mtDNA variants were impeded by a lack of adequate tumor mtDNA sequencing data and available methods for mitochondrial genome engineering. These barriers and a conceptual fog surrounding the functional impact of mtDNA mutations in tumors have begun to lift, revealing a path to understanding the role of this essential metabolic genome in cancer initiation and progression. Here we discuss the history, recent developments, and challenges that remain for mitochondrial oncogenetics as the impact of a major new class of cancer-associated mutations is unveiled. Mitochondrial DNA (mtDNA) mutations are among the most common genetic events in all tumors and directly impact metabolic homeostasis. Despite the central role mitochondria play in energy metabolism and cellular physiology, the role of mutations in the mitochondrial genomes of tumors has been contentious. Until recently, genomic and functional studies of mtDNA variants were impeded by a lack of adequate tumor mtDNA sequencing data and available methods for mitochondrial genome engineering. These barriers and a conceptual fog surrounding the functional impact of mtDNA mutations in tumors have begun to lift, revealing a path to understanding the role of this essential metabolic genome in cancer initiation and progression. Here we discuss the history, recent developments, and challenges that remain for mitochondrial oncogenetics as the impact of a major new class of cancer-associated mutations is unveiled.
Responding to the Escalating Cybersecurity Threat to Health Care
Authors: Eric Perakslis
Journal: New England Journal of Medicine (2022)

Interview with Dr. Eric Perakslis on cybersecurity threats to patients and health care systems. (08:47)Download The cyberthreat to health care has never been greater. Fortunately, clinicians can protect themselves and their patients from the worst of these attacks, in part by means of precautions and preparation.
Concurrent Zrsr2 mutation and Tet2 loss promote myelodysplastic neoplasm in mice
Authors: Cristian Garcia-Ruiz, Cristina Martínez-Valiente, Lourdes Cordón, Alessandro Liquori, Raúl Fernández-González, Eva Pericuesta, Juan Sandoval, José Cervera, Alfonso Gutiérrez-Adán, Alejandra Sanjuan-Pla
Journal: Leukemia (2022)

Abstract RNA splicing and epigenetic gene mutations are the most frequent genetic lesions found in patients with myelodysplastic neoplasm (MDS). About 25% of patients present concomitant mutations in such pathways, suggesting a cooperative role in MDS pathogenesis. Importantly, mutations in the splicing factor ZRSR2 frequently associate with alterations in the epigenetic regulator TET2 . However, the impact of these concurrent mutations in hematopoiesis and MDS remains unclear. Using CRISPR/Cas9 genetically engineered mice, we demonstrate that Zrsr2 m/m Tet2 −/− promote MDS with reduced penetrance. Animals presented peripheral blood cytopenia, splenomegaly, extramedullary hematopoiesis, and multi-lineage dysplasia, signs consistent with MDS. We identified a myelo-erythroid differentiation block accompanied by an expansion of LT-HSC and MPP2 progenitors. Transplanted animals presented a similar phenotype, thus indicating that alterations were cell-autonomous. Whole-transcriptome analysis in HSPC revealed key alterations in ribosome, inflammation, and migration/motility processes. Moreover, we found the MAPK pathway as the most affected target by mRNA aberrant splicing. Collectively, this study shows that concomitant Zrsr2 mutation and Tet2 loss are sufficient to initiate MDS in mice. Understanding this mechanistic interplay will be crucial for the identification of novel therapeutic targets in the spliceosome/epigenetic MDS subgroup.
Response to “The WHO classification of haematolymphoid tumours” (Editorial)
Authors: Steven H. Swerdlow, Elias Campo, Daniel A. Arber, Mario Cazzola, James R. Cook, Hartmut Döhner, Martin Dreyling, Robert P. Hasserjian, Elaine S. Jaffe, Attilio Orazi, Leticia Quintanilla-Martinez, David W. Scott, Ayalew Tefferi, Jane N. Winter, Andrew D. Zelenetz
Journal: Leukemia (2022)
Stillbirth After Adolescent and Young Adult Cancer: A Population-Based Study
Authors: Caitlin C Murphy, Andrea C Betts, Marlyn A Allicock, L Aubree Shay, Sharice M Preston, Barbara A Cohn, Philip J Lupo, Sandi L Pruitt
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background Gonadotoxic effects of cancer treatment may increase risk of adverse birth outcomes in adolescent and young adult (AYA, aged 15-39 years) women diagnosed with cancer. We estimated risk of stillbirth (fetal death of gestational age ≥20 weeks or weighing ≥350 grams) in a population-based sample of AYA women. Methods AYA women diagnosed with cancer between January 1, 1995, and December 31, 2015, were identified using the Texas Cancer Registry and linked to live birth and fetal death certificates through December 31, 2016. Among AYA women, cumulative incidence of stillbirth was estimated by gestational age, and Poisson regression models identified factors associated with stillbirth. Standardized fetal mortality ratios (SMR) compared the observed fetal mortality rate in AYA women with the expected fetal mortality rate in the general population. Results A total of 11 628 live births and 68 stillbirths occurred to 8402 AYA women after diagnosis. Cumulative incidence of stillbirth in AYA women was 0.70% (95% confidence interval [CI] = 0.51% to 0.96%) at 40 weeks of gestation. Risk of stillbirth was higher among Hispanic (risk ratio [RR] = 2.64, 95% CI = 1.29 to 5.41) and non-Hispanic Black (RR = 4.13, 95% CI = 1.68 to 10.16) women compared with non-Hispanic White women; there was no association with receipt of chemotherapy or time since diagnosis. Age- and race and ethnicity–adjusted fetal mortality rate in AYA women was similar to the general population (SMR = 0.99, 95% CI = 0.77 to 1.26). Conclusions AYA women may be counseled that overall risk of stillbirth is low, and for most, cancer does not appear to confer additional risk.
Risk of Pancreatic Cancer in the Long-Term Prospective Follow-Up of Familial Pancreatic Cancer Kindreds
Authors: Nancy Porter, Daniel Laheru, Bryan Lau, Jin He, Lei Zheng, Amol Narang, Nicholas J Roberts, Marcia I Canto, Anne Marie Lennon, Michael G Goggins, Ralph H Hruban, Alison P Klein
Journal: JNCI Journal of the National Cancer Institute (2022)

A family history of pancreatic cancer is associated with increased pancreatic cancer risk. However, risk estimates for individuals in kindreds with an aggregation of pancreatic cancer (>1 relative) are imprecise because of small samples sizes or potentially impacted by biases inherent in retrospective data.
Cancer Hazard Evaluations for Contemporary Needs: Highlights From New National Toxicology Program Evaluations and Methodological Advancements
Authors: Ruth M Lunn, Suril S Mehta, Gloria D Jahnke, Amy Wang, Mary S Wolfe, Brian R Berridge
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract The National Toxicology Program strives to raise awareness of cancer hazards in our environment. Identifying cancer hazards is key to primary prevention, informing public health decision making, and decreasing the global cancer burden. In December 2021, the US congressionally mandated 15th Report on Carcinogens was released, adding 8 new substances to the cumulative report. Chronic infection with Helicobacter pylori is listed as “known to be a human carcinogen.” Antimony trioxide and 6 haloacetic acids found as water disinfection by-products—dichloroacetic acid, dibromoacetic acid, bromochloroacetic acid, tribromoacetic acid, bromodichloroacetic acid, chlorodibromoacetic acid—are listed as “reasonably anticipated to be a human carcinogen.” A new dashboard provides interactive visualization and interrogation of the 256 listed substances, their uses, and associated cancers. Also, the National Toxicology Program recently published a Cancer Hazard Assessment Report on exposure scenarios associated with circadian disruption, concluding that persistent night shift work can cause breast cancer and certain lighting conditions may cause cancer. As highlighted in these reports and evaluations, we are evolving our approaches to meet contemporary challenges. These approaches include focusing on real-world exposures and advancing our methods to address challenges in cancer hazard assessments (eg, developing more structured approaches to evaluate mechanistic data and incorporating read-across approaches to assess chemicals lacking adequate human or animal cancer data). To promote public health, we provide information on environmental health disparities and disease prevention. Building on these efforts, we aim to continue our contributions to the war on cancer, declared 50 years ago.
Apoptotic vesicles ameliorate lupus and arthritis via phosphatidylserine-mediated modulation of T cell receptor signaling
Authors: Runci Wang, Meng Hao, Xiaoxing Kou, Bingdong Sui, Maria Laura Sanmillan, Xiao Zhang, Dawei Liu, Jun Tian, Wenjing Yu, Chider Chen, Ruili Yang, Lingyun Sun, Yi Liu, Claudio Giraudo, Deepak A. Rao, Nan Shen, Songtao Shi
Journal: Bioactive Materials (2022)

Mesenchymal stem cells (MSCs) influence T cells in health, disease and therapy through messengers of intercellular communication including extracellular vesicles (EVs). Apoptosis is a mode of cell death that tends to promote immune tolerance, and a large number of apoptotic vesicles (apoVs) are generated from MSCs during apoptosis. In an effort to characterize these apoVs and explore their immunomodulatory potential, here we show that after replenishing them systemically, the apoV deficiency in Fas mutant mice and pathological lymphoproliferation were rescued, leading to the amelioration of inflammation and lupus activity. ApoVs directly interacted with CD4+ T cells and inhibited CD25 expression and IL-2 production in a dose-dependent manner. A broad range of Th1/2/17 subsets and cytokines including IFNγ, IL17A and IL-10 were suppressed while Foxp3+ cells were maintained. Mechanistically, exposed phosphatidylserine (PtdSer/PS) on apoVs mediated the interaction with T cells to disrupt proximal T cell receptor signaling transduction. Remarkably, administration of apoVs prevented Th17 differentiation and memory formation, and ameliorated inflammation and joint erosion in murine arthritis. Collectively, our findings unveil a previously unrecognized crosstalk between MSC apoVs and CD4+ T cells and suggest a promising therapeutic use of apoVs for autoimmune diseases.
An update on viral-induced cutaneous lymphoproliferative disorders. CME Part I
Authors: Jose A. Plaza, Alejandro A. Gru, Omar P. Sangueza, Silvia V. Lourenco, Francisco B. Puccio, Jose A. Sanches, Denis Miyashiro, Sonia Toussaint, Martin J. Sangueza
Journal: Journal of the American Academy of Dermatology (2022)
Evidence-based consensus guidelines for the diagnosis and management of erythropoietic protoporphyria and X-linked protoporphyria
Authors: Amy K. Dickey, Hetanshi Naik, Siobán B. Keel, Cynthia Levy, Simon W. Beaven, Sarina B. Elmariah, Angelika L. Erwin, Robert J. Goddu, Karli Hedstrom, Rebecca K. Leaf, Mohamed Kazamel, Marshall Mazepa, Lisa Liang Philpotts, John Quigley, Haya Raef, Sean R. Rudnick, Behnam Saberi, Manish Thapar, Jonathan Ungar, Bruce Wang, Manisha Balwani
Journal: Journal of the American Academy of Dermatology (2022)
Phase 2 randomized clinical trial of astegolimab in patients with moderate to severe atopic dermatitis
Authors: Marcus Maurer, Dorothy S. Cheung, Wiebke Theess, Xiaoying Yang, Michael Dolton, Anna Guttman, David F. Choy, Ajit Dash, Michele A. Grimbaldeston, Weily Soong
Journal: Journal of Allergy and Clinical Immunology (2022)
Autoimmune diseases and cardiovascular risk: a population-based study on 19 autoimmune diseases and 12 cardiovascular diseases in 22 million individuals in the UK
Authors: Nathalie Conrad, Geert Verbeke, Geert Molenberghs, Laura Goetschalckx, Thomas Callender, Geraldine Cambridge, Justin C Mason, Kazem Rahimi, John J V McMurray, Jan Y Verbakel
Journal: The Lancet (2022)
Determinants of lung function across childhood in the Severe Asthma Research Program (SARP) 3
Authors: Jonathan M. Gaffin, Carter R. Petty, Ronald L. Sorkness, Loren C. Denlinger, Brenda R. Phillips, Ngoc P. Ly, Benjamin Gaston, Kristie Ross, Anne Fitzpatrick, Leonard B. Bacharier, Mark D. DeBoer, W. Gerald Teague, Sally E. Wenzel, Sima Ramratnam, Elliot Israel, David T. Mauger, Wanda Phipatanakul
Journal: Journal of Allergy and Clinical Immunology (2022)
Estimated Long-Term Benefit of Dapagliflozin in Patients With Heart Failure
Authors: Muthiah Vaduganathan, Brian L. Claggett, Pardeep Jhund, Rudolf A. de Boer, Adrian F. Hernandez, Silvio E. Inzucchi, Mikhail N. Kosiborod, Carolyn S.P. Lam, Felipe Martinez, Sanjiv J. Shah, Akshay S. Desai, Daniel Lindholm, Magnus Petersson, Anna Maria Langkilde, John J.V. McMurray, Scott D. Solomon
Journal: Journal of the American College of Cardiology (2022)

Recent guidelines support consideration of sodium-glucose cotransporter-2 inhibitors in the long-term management of heart failure (HF) with mildly reduced or preserved ejection fraction. Patients and clinicians may be interested in the expected lifetime benefits of sodium-glucose cotransporter-2 inhibitors in this population.This study aimed to estimate event-free survival gains from long-term use of dapagliflozin in patients with HF with mildly reduced or preserved ejection fraction overall and in clinically relevant subgroups.In this prespecified analysis of DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure), we applied validated nonparametric age-based methods to extrapolate potential gains in survival free from the primary endpoint (cardiovascular death or worsening HF event) from long-term use of dapagliflozin. Eligible participants had symptomatic HF, left ventricular ejection fraction >40%, elevated natriuretic peptide levels, and structural heart disease. For every year between the ages of 55 and 85 years, we estimated event-free survival using age at randomization rather than time from randomization as the time horizon. Residual lifespan free from a primary endpoint was estimated based on area under the survival curve in each arm.Among 6,263 participants, mean survival free from the primary endpoint for a 65-year-old participant was 12.1 years (95% CI: 11.0-13.2 years) with dapagliflozin and 9.7 years (95% CI: 8.8-10.7 years) with placebo, representing a 2.3-year (95% CI: 0.9-3.8 years) event-free survival gain (P = 0.002). Treatment gains in survival free from the primary endpoint ranged from 2.0 years (95% CI: -0.6 to 4.6 years) in a 55-year-old to 1.2 years (95% CI: -0.1 to 2.4 years) in a 75-year-old patient. Mean event-free survival was greater with dapagliflozin than with placebo across all 14 subgroups.Treatment with dapagliflozin is projected to extend event-free survival by up to 2.0 to 2.5 years among middle-aged and older individuals with HF with mildly reduced or preserved ejection fraction. (DELIVER [Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure]; NCT03619213).